Targeted isolation of antitubercular cycloheptapeptides and an unusual pyrroloindoline-containing new analog, asperpyrroindotide A, using LC–MS/MS-based molecular networking
Yi-Qian Han, Qun Zhang, Weifeng Xu, Yang Hai, Rong Chao, Cuifang Wang, Xuemei Hou, Mei‐Yan Wei, Yu‐Cheng Gu, Chang‐Yun Wang, Chang‐Lun Shao
Abstract
Abstract Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides, namely, asperversiamides A–C ( 1 – 3 ) and asperheptatides A–D ( 4 – 7 ) and an unusual pyrroloindoline-containing new cycloheptapeptide, asperpyrroindotide A ( 8 ). The structure of 8 was elucidated by comprehensive spectroscopic data analysis, and its absolute configuration was determined by advanced Marfey’s method. The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized. Additionally, a series of new derivatives ( 10 − 19 ) of asperversiamide A ( 1 ) was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra. The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.